Abstract / Project Summary Numerous studies have found that Black women are more likely than White women to be diagnosed with estrogen receptor negative (ER-) breast cancer subtypes. ER- tumors are frequently larger and more advanced at the time of diagnosis, and they are not responsive to current endocrine-based treatments. A smaller body of research suggests that, across racial/ethnic groups, women from lower socioeconomic status (SES) areas also have higher rates of ER- breast cancer. Broader social forces that shape the relationship between individual race and socioeconomic factors could independently contribute to the observed disparity in breast cancer subtypes, but these relationships have not been adequately examined. New transdisciplinary approaches that better integrate current knowledge of ER- breast cancer molecular biology, ER- epidemiological risk factors such as parity and breast feeding history, and social inequalities (e.g., disparate state-level college graduation rates among males and females, or among White and Black women) that are germane to both race and SES are needed to fill this substantial knowledge gap. Dr. Linnenbringer's career goal is to become an independent researcher who is uniquely positioned to develop, conduct, and communicate research bridging breast cancer biology, genetic epidemiology, and socio-behavioral sciences. Her research experience and prior training in genetic counseling, health behavior theory, and social demography provide a unique foundation for her proposed research. In the proposed training plan, Dr. Linnenbringer will develop additional skills in next-generation genomic analysis techniques, genetic epidemiology research methods, and breast cancer molecular biology. Her training will be directly applied to support and advance the proposed research plan and her career as an independent researcher. Leveraging the uniquely rich set of social, behavioral, genomic, and breast cancer outcome data available in a prospective cohort of over 50,000 women (The Sister Study), Dr. Linnenbringer's proposed research will: 1) examine direct and indirect associations between measures of social inequality and subtype-specific breast cancer incidence, 2) examine possible gene-environment interactions (GxE) interactions between social inequality and single nucleotide polymorphisms (SNPs) that have been previously established as ER- breast cancer risk modifiers and reside within genetic pathways that are potentially sensitive to elements in the social environment, and 3) assess gene-environment correlation (rGE) among percentage of African genetic ancestry, measures of racial inequality, and subtype-specific breast cancer incidence. Results from this study will provide a more nuanced assessment of the complex social, behavioral, and genomic factors associated with ER- breast cancer. With this training and experience, Dr. Linnenbringer will be well positioned to launch her independent research career, conducting innovative transdisciplinary research and effectively communicating the complexity of its results.